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许琛琦，研究员，研究组长，博士生导师。1998年获得华东师范大学生物化学专业理学学士；2001年获得华东师范大学与中科院生化所联合培养理学硕士；2004年获得中科院生物化学与细胞生物学研究所理学博士。2004年赴美国哈佛大学医学院Dana-Farber肿瘤研究所从事免疫学研究，先后为博士后(受美国关节炎基金会资助)，instructor。2009年11月回生化与细胞所工作，担任研究员，研究组长。2005年获上海市科技进步一等奖，2010年获中科院百人计划以及上海市浦江人才计划资助，2013年获中科院青年科学家奖。

Plasma member is an asymmetrical lipid bilayer environment and its inner-leaflet is enriched of acidic phospholipids. The negatively charged acidic phospholipids interact with positively charged proteins and thus regulate critical signaling events. We are studying how the ionic protein-lipid interaction regulates the activation of T-cell receptor (TCR), a key immunoreceptor that recognizes antigen and initiates the adaptive immune responses against invading pathogens. TCR is composed of four subunits: the antigen recognition subunit TCR and signaling subunits CD3, and Antigen binding on the TCR subunit generates mechanical force and this physical signal can be transduced across the membrane and decoded to CD3 tyrosine phosphorylation signal. The molecular mechanism of this physical-to-chemical signal transduction process remains elusive. The cytoplasmic domains of CD3 and chains (CD3CD and CD3CD) are enriched of basic residues and we and other groups find that CD3CD and CD3CD interact with the acidic phospholipids in the plasma membrane. The key tyrosine residues in CD3CD and CD3CD are fully embedded in the hydrophobic core of the membrane bilayer, which prevents the spontaneous phosphorylation of CD3 chains in quiescent T cells. After T cells are stimulated by antigens, Ca2+ ions locally influx into T cells and generate Ca2+ microdomains proximal to TCRs. We find that Ca2+ ions can directly bind to the acidic phospholipids and neutralize their negative charges, which in turn disrupts the ionic CD3-lipid interaction and lead to the solvent exposure of the key tyrosine residues. Ca2+ can thus help CD3 phosphorylation and amplify the weak antigen-stimulating signal to fully activate T cells. These studies demonstrate that membrane lipids can sequester TCR activation sites at quiescent stage, whereas Ca2+ can release these activation sites for phosphorylation in antigen-stimulated T cells. We find that this tyrosine sequestration-release mechanism is also applicable to other immunoreceptors.